Cell atlas of CCl_(4)-induced progressive liver fibrosis reveals stage-specific responses

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality worldwide.However,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis stages.To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver fibrosis.Integrative analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial cells.Moreover,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these processes.These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver fibrosis.Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

Effect of welding sequence on residual stress and deformation of 6061-T6 aluminium alloy automobile component

Four different welding sequences of double-pulse MIG welding were conducted for 6061-T6 aluminum alloy automobile bumpers by using nonlinear elastoplasticity finite element method based on ABAQUS software.The post-welding residual stress and deformation were definitely different among the four welding sequences.The results showed that the highest temperature in Solution A was approximately 200℃higher than the melting point of base metal.High residual stress was resulted from this large temperature gradient and mainly concentrated on the welding vicinity between beam and crash box.The welding deformation primarily occurred in both of the contraction of two-ends of the beam and the self-contraction of crash box.Compared with other welding sequences,the residual stress in Solution A was the smallest,whereas the welding deformation was the largest.However,the optimal sequence was Solution B because of the effective reduction of residual stress and good assembly requirements.

Abnormal Twinning Behavior and Constitutive Modeling of a Fine-Grained Extruded Mg-8.0Al-0.1Mn-2.0Ca Alloy under High-Speed Impact along Various Directions

To understand the mechanical and twinning behaviors of a fine-grained extruded Mg-8.0Al-0.1Mn-2.0Ca alloy under high-speed impact,impact tests were carried out using a split Hopkinson pressure bar,and microstructures at strains of 0.05,0.10 and 0.20 were obtained using a series of stop rings manufactured by high-strength steel.The stress response and twinning behavior are closely related to loading direction and applied strain rate.The true stress-true strain curves are s-shaped in extrusion direction(ED)and c-shaped in transverse direction(TD),showing apparent anisotropy,while the yield strength is insensitive to loading direction.Almost identical strain-rate sensitivity is demonstrated by the stress in ED and TD.Interestingly,de-twinning is apparent as the applied strain increases to 0.20,and it is enhanced with increasing the applied strain rate.In contrast,the twin density in ED samples is clearly higher than that in TD samples.By modifying the terms of strain hardening and strain rate hardening in the classical JC model,an optimized model is built,which can accurately predict the stress response behavior of the studied alloy under high-speed impact along ED and TD.The correlation coefficient(R)and average absolute relative error(AARE)are 98.63%and 0.0199 for ED,and 96.88%and 0.0202 for TD,respectively.

Numerical investigation of alleviation of undesirable effect of inter-blade vortex with air admission for a low-head Francis turbine

In order to compensate for the stochastic nature of the power grid due to the tremendous development and the integration of renewable energy resources and meet its other requirements,the hydraulic turbines are forced to operate more frequently under partial load conditions with singular and misaligned flows inevitably excited by the inter-blade vortex.This paper presents numerical investigations of the unsteady characteristics of the inter-blade vortex for a low-head model Francis turbine.The SST k-ωturbulent model is used to close the unsteady Reynolds-averaged Navier-Stokes(RANS)equation.The flow structure of the inter blade vortex predicted by the numerical simulation is confirmed by experimental visualizations.It is shown that the total vortex volume in the runner sees a quasi-periodical oscillation,with significant flow separations created on the suction side of the runner blade.A counter measure by using the air admission into the water from the head cover is implemented to alleviate the undesirable effect of the inter-blade vortex.The analyses show that the development of the inter-blade vortex is significantly mitigated by the injecting air that controls and changes the spatial distribution of streamlines.Furthermore,the flow aeration with a suitable air flow rate can reduce the energy dissipation caused by the inter-blade vortex and plays a critical role in preventing the excessive amplitudes of the pressure fluctuation on the suction side of the runner blade.This investigation provides an insight into the flow mechanism underlying the inter-blade vortex and offers a reference to alleviate and mitigate the adverse consequences of the inter-blade vortex for the Francis turbine.

Numerical investigation of the effect of T-shaped blade on the energy performance improvement of a semi-open centrifugal pump

The tip leakage flow formed by the tip clearance of a semi-open centrifugal pump adversely affects the energy performance and the energy waste. A T-shaped blade is proposed to be used to improve the energy characteristics. The internal flow field is simulated via the shear stress transport turbulence model to analyze the influence of the T-shaped blade on the performance of a centrifugal pump. It is shown that with the T-shaped blade, the hydraulic loss can be reduced, the Euler head can be increased, and the external characteristics can be improved. The maximum head and efficiency improvements are 3% and 1.6%, respectively. The relative flow angle near the tip clearance of the T-shaped blade decreases, and the strength of the backflow region is remarkably weakened. The area of the high entropy production region decreases, and the trend of the upstream diffusion is restrained under the design condition. The T-shaped blade can help to inhibit the diffusion of the high entropy production region to the hub under the low flow rate condition, but the entropy production and the mixing losses at the tip clearance are slightly increased. This research provides a new method for improving the energy performance of the semi-open centrifugal pump.